Navigation Links
One gene, many mutations

For deer mice living in the Nebraska Sandhills, color can literally be the difference between life and death.

When they first colonized the region, the dark-coated mice stood out starkly against the light-colored, sandy soil, making them easy prey for predators. Over the next 8,000 years, however, the mice evolved a new system of camouflage lighter coats, changes in the stripe on their tails and changes in the extent of pigment across their body that allowed them to blend into their new habitat.

Now Harvard researchers are using their example to answer one of the fundamental questions about evolution - is it a process marked by large leaps single mutations that result in dramatic change in an organism or is it the result of many smaller changes that accumulate over time?

As described in a March 15 paper in Science, a team of researchers, including former Postdoctoral Fellow Catherine Linnen, now an Assistant Professor at the University of Kentucky, and led by Professor of Organismic and Evolutionary Biology and Molecular and Cellular Biology Hopi Hoekstra, were able to show that the changes in mouse coat color were the result not of a single mutation, but at least nine separate mutations all within a single gene.

"The findings demonstrate how the cumulative effect of natural selection, acting on many small genetic changes, can produce rapid and dramatic change," Linnen, the first author of the paper, said. "This helps us to understand, from a genetic perspective, the uncanny fit between so many organisms and their environmentsby acting on many small changes, rather than a handful of large ones, natural selection can produce very finely honed adaptations."

Surprisingly, Hoekstra said, that honing occurred in a single gene.

The role of this gene, called agouti, in camouflage was first discovered by Linnen, Hoekstra and colleagues in 2009, and it is responsible for changes in pigmentation in the coats of many animals. Every domesticated black cat, for example, has a DNA deletion in the gene.

What surprised Hoekstra and her team, however, wasn't that the gene was involved, but that each of the nine mutations were tied to a unique change in the animal's coats, that all the new mutations led to more camouflaging color, and that the mutations occurred in a relatively short, 8,000-year timeframe.

"Essentially, it seems as though these mutations each of which makes the mouse a little lighter and more camouflaged have accumulated over time," Hoekstra said.

Focusing on these mutations, researchers then examined the DNA of natural populations of the mice to determine whether the mutations are actually beneficial.

"For each of the mutations associated with color change, we also find a signal that's consistent with positive selection," Hoekstra said. "That implies that each of the specific changes to pigmentation is beneficial. This is consistent with the story we are telling about how these mutations are fine-tuning this trait."

While the findings offer valuable insight into the way natural selection operates, Hoekstra said they also highlight the importance of following research questions to their ultimate end.

"The question has always been whether evolution is dominated by these big leaps or smaller steps," she said. "When we first implicated the agouti gene, we could have stopped there and concluded that evolution takes these big steps as only one major gene was involved, but that would have been wrong. When we looked more closely, within this gene, we found that even within this single locus, there are, in fact, many small steps."

Going forward, Hoekstra said, her team hopes to understand the order in which the mutations happened, which would allow them to reconstruct how the mice changed over time.

"For evolutionary biologists, this is exciting because we want to learn about the past, but we only have data from the present to study it," she said. "This ability to go back in time and reconstruct an evolutionary path is very exciting, and I think this data set is uniquely suited for this type of time travel."

Taking the time to understand not only which genes are involved, but which specific mutations may be driving natural selection, Hoekstra said, can give researchers a much fuller picture of not only the molecular mechanisms by which mutations alter traits, but also the evolutionary history of an organism as well.

"By doing this we've discovered all kinds of new things," she said. "While we often think about changes happening in the entire genome, our results suggest that even within a very basic unit the gene we can see evidence for evolutionary fine-tuning."


Contact: Peter Reuell
Harvard University

Related biology news :

1. BRG1 mutations confer resistance to hormones in lung cancer
2. Gene mutations cause massive brain asymmetry
3. Interacting mutations promote diversity
4. Mutations in autism susceptibility gene increase risk in boys
5. UMMS researchers isolate gene mutations in patients with inherited amyotrophic lateral sclerosis
6. New gene mutations linked to ALS and nerve cell growth dysfunction
7. Key mutations discovered for most common childhood brain cancer
8. BGI reports the latest finding on NMNAT1 mutations linked to Leber congenital amaurosis
9. Gene mutations linked to most cases of rare disorder -- Alternating Hemoplegia of Childhood
10. New method provides fast, accurate, low cost analysis of BRCA gene mutations in breast cancer
11. Populations survive despite many deleterious mutations
Post Your Comments:
(Date:11/17/2015)... Paris from 17 th until ... from 17 th until 19 th November ... has invented the first combined scanner in the world which scans ... Until now two different scanners were required: one for passports ... on the same surface. This innovation is an ideal solution ...
(Date:11/17/2015)... EASTON, Mass. , Nov. 17, 2015 ... a leader in the development and sale of broadly ... the worldwide life sciences industry, today announced it has ... of its $5 million Private Placement (the "Offering"), increasing ... to $4,025,000.  One or more additional closings are expected ...
(Date:11/12/2015)... Nov. 12, 2015  Arxspan has entered into ... and Harvard for use of its ArxLab cloud-based ... tools. The partnership will support the institute,s efforts ... chemical research information internally and with external collaborators. ... for managing the Institute,s electronic laboratory notebook, compound ...
Breaking Biology News(10 mins):
(Date:11/24/2015)... , Nov. 24, 2015  Tikcro Technologies Ltd. (OTCQB: TIKRF) today ... December 29, 2015 at 11:00 a.m. Israel time, ... Tower, 98 Yigal Allon Street, 36 th Floor, Tel ... Eric Paneth and Izhak Tamir to the Board ... Skaliter as external directors; , approval of an amendment to certain ...
(Date:11/24/2015)... , Nov. 24, 2015  Twist Bioscience, ... that Emily Leproust, Ph.D., Twist Bioscience chief executive ... Healthcare Conference on December 1, 2015 at 3:10 ... in New York City. --> ... . Twist Bioscience is on Twitter. Sign ...
(Date:11/24/2015)... ... November 24, 2015 , ... InSphero AG, the leading supplier of ... has promoted Melanie Aregger to serve as Chief Operating Officer. , Having ... management team and was promoted to Head of InSphero Diagnostics in 2014. ...
(Date:11/24/2015)... , Nov. 24, 2015 /CNW Telbec/ - ProMetic Life Sciences ... today that Mr. Pierre Laurin , President and Chief ... at the upcoming Piper Jaffray 27 th Annual Healthcare ... on December 1-2, 2015. st , at ... one-on-one meetings throughout the day. The presentation will be available ...
Breaking Biology Technology: